Data demonstrated C101248 is a promising inhibitor of THIK-1, an emerging target in Alzheimer’s disease.
THIK-1 was identified using Cerevance’s proprietary NETSseq platform.
Boston, MA – November 15, 2022 – Cerevance, a private, clinical-stage drug discovery and development company focused on central nervous system (CNS) diseases, announced the presentation of preclinical study results during the poster session held November 14th at the Society for Neuroscience (SFN) 2022 conference in San Diego, California.
“We are incredibly pleased to have identified not only a new target for the treatment of Alzheimer’s disease, but also a means to inhibit inflammatory signaling associated with THIK-1 in cellular models,” said Mark Carlton, Ph.D., chief scientific officer of Cerevance. “NETSseq is a powerful tool to identify previously unelucidated drug targets for the development of novel therapies.”
The presentation entitled “Identification of THIK-1 as a Therapeutic Target For Alzheimer’s Disease: Characterization of a Selective and Novel Blocker,” demonstrated the power of the proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) platform in identifying a novel target.
Key highlights of the presentation include:
- Using NETSseq, tandem pore domain halothane-inhibited potassium channel 1 (THIK-1) demonstrated significantly restricted gene expression in microglia which is increased in Alzheimer’s diseased human brain samples.
- C101248, Cerevance’s novel inhibitor, demonstrated a concentration-dependent inhibition of the protein in human and mouse cells expressing THIK-1 with similar potency and maximum effect as measured by thalium assays and patch-clamp experiments.
- Inhibition of THIK-1 with C101248 resulted in reduced activity of the NLRP3 inflammasome and a reduction of the cytokine IL-1β, key components in the development of neuroinflammation in Alzheimer’s disease.
- Overall, the data demonstrate the promise of blocking the target THIK-1 with molecules such as C101248 for the treatment of Alzheimer’s disease.
Cerevance’s proprietary NETSseq approach enables the company to comprehensively profile specific brain cell types – including both neurons and glial cells – in mature human brain tissue. The approach involves using antibodies against nuclear proteins (e.g., transcription factors), endoplasmic reticulum proteins and membrane proteins, as well as RNA probes against any cell-type-specific transcripts. These probes tag specific cell types in brain tissue to enable the sorting of nuclei using fluorescence-activated cell sorting (FACS).
Cerevance is a private pharmaceutical company whose lead therapeutic, CVN424, a first-in-class, oral, non-dopaminergic compound acting on a novel target (GPR6), recently demonstrated significant and clinically meaningful efficacy in a 135-patient Phase 2 study in patients with Parkinson’s disease. The company uses its proprietary NETSseq technology platform to identify highly selectively novel target proteins that are either specific to certain brain circuits or are over- or under-expressed in diseased brains. Partnering with over 25 brain banks and evaluating more than 12,000 human post-mortem brain tissue samples, Cerevance is advancing a robust pipeline of targeted treatments for patients with neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. For additional information, please visit www.cerevance.com.
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